title: Investigations of caspr2, an autoantigen of encephalitis and neuromyotonia.
abstract: OBJECTIVE
  To report clinical and immunological investigations of contactin-associated protein-like 2 (Caspr2), an autoantigen of encephalitis and peripheral nerve hyperexcitability (PNH) previously attributed to voltage-gated potassium channels (VGKC).
  
  
  METHODS
  Clinical analysis was performed on patients with encephalitis, PNH, or both. Immunoprecipitation and mass spectrometry were used to identify the antigen and to develop an assay with Caspr2-expressing cells. Immunoabsorption with Caspr2 and comparative immunostaining of brain and peripheral nerve of wild-type and Caspr2-null mice were used to assess antibody specificity.
  
  
  RESULTS
  Using Caspr2-expressing cells, antibodies were identified in 8 patients but not in 140 patients with several types of autoimmune or viral encephalitis, PNH, or mutations of the Caspr2-encoding gene. Patients' antibodies reacted with brain and peripheral nerve in a pattern that colocalized with Caspr2. This reactivity was abrogated after immunoabsorption with Caspr2 and was absent in tissues from Caspr2-null mice. Of the 8 patients with Caspr2 antibodies, 7 had encephalopathy or seizures, 5 neuropathy or PNH, and 1 isolated PNH. Three patients also had myasthenia gravis, bulbar weakness, or symptoms that initially suggested motor neuron disease. None of the patients had active cancer; 7 responded to immunotherapy and were healthy or only mildly disabled at last follow-up (median, 8 months; range, 6-84 months).
  
  
  CONCLUSIONS
  Caspr2 is an autoantigen of encephalitis and PNH previously attributed to VGKC antibodies. The occurrence of other autoantibodies may result in a complex syndrome that at presentation could be mistaken for a motor neuron disorder. Recognition of this disorder is important, because it responds to immunotherapy.
authors.affiliation: Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Lancaster
authors.forename: Maartje G M
authors.initials: MG
authors.lastname: Huijbers
authors.forename: Vered
authors.initials: V
authors.lastname: Bar
authors.forename: Anna
authors.initials: A
authors.lastname: Boronat
authors.forename: Andrew
authors.initials: A
authors.lastname: Wong
authors.forename: Eugenia
authors.initials: E
authors.lastname: Martinez-Hernandez
authors.forename: Christina
authors.initials: C
authors.lastname: Wilson
authors.forename: Dina
authors.initials: D
authors.lastname: Jacobs
authors.forename: Meizan
authors.initials: M
authors.lastname: Lai
authors.forename: Russell W
authors.initials: RW
authors.lastname: Walker
authors.forename: Francesc
authors.initials: F
authors.lastname: Graus
authors.forename: Luis
authors.initials: L
authors.lastname: Bataller
authors.forename: Isabel
authors.initials: I
authors.lastname: Illa
authors.forename: Sander
authors.initials: S
authors.lastname: Markx
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Strauss
authors.forename: Elior
authors.initials: E
authors.lastname: Peles
authors.forename: Steven S
authors.initials: SS
authors.lastname: Scherer
authors.forename: Josep
authors.initials: J
authors.lastname: Dalmau
mesh_terms: D000368:Aged; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D004660:Encephalitis / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D020386:Isaacs Syndrome / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology*; D010525:Peripheral Nerves / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; C403049:CNTNAP2 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins